title: Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition.
abstract: The epithelial-mesenchymal transition (EMT) is a process in which polarized epithelial cells are converted into motile mesenchymal cells. During cancer development, EMT is conducive to tumor dissemination and metastatic spread. While overexpression of metadherin (MTDH) in breast cancer cell lines and tissues has been found to be associated with aggressive tumor behavior, its precise role in invasion and metastasis is largely unknown. Here we report that MTDH overexpression could significantly enhance the invasion and migration of breast cancer cells by inducing EMT. Metadherin overexpression led to upregulation of mesenchymal marker fibronectin, downregulation of epithelial marker E-cadherin, and the nuclear accumulation of beta-catenin. Also, transcription factors Snail and Slug were upregulated in breast cancer cells overexpressing MTDH. Overexpression of MTDH enhanced the invasiveness and migration ability of breast cancer cells in vitro. In addition, overexpression of MTDH led to increased acquisition of CD44(+) /CD24(-/low) markers that are characteristic of breast cancer stem cells. We also showed that NF-kappa was involved in the expression of EMT-related markers. Taken together, our results suggest that MTDH could promote EMT in breast cancer cells in driving the progression of their aggressive behavior.
authors.affiliation: Department of Breast Surgery, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Kong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huo
authors.forename: Haiyang
authors.initials: H
authors.lastname: Guo
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.forename: Cunzhong
authors.initials: C
authors.lastname: Yuan
authors.forename: Meena S
authors.initials: MS
authors.lastname: Moran
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D051927:CD24 Antigen; D015820:Cadherins / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells; D034622:RNA Interference; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D051927:CD24 Antigen; D015820:Cadherins; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D018960:Hyaluronan Receptors; C483039:MTDH protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin